Men who have sex with men (MSM) remain a major priority for HIV prevention, comprising the majority of reported AIDS cases in North and South America. The University of Washington, in collaboration with Universidad Peruana Cayetano Heredia in Lima, proposes to conduct HIV prevention research among high-risk MSM in Seattle and Peru with a focus on STDs and rectal inflammation that could increase HIV transmission among MSM. The investigators propose to conduct a randomized STD prevention trial in Peru to reduce HIV acquisition in MSM. Such an intervention could also have significant impact on STD and HIV transmission to women, given the high proportion of high-risk MSM who report recent unprotected vaginal sex and may serve as a potential "bridging" population to women. Specific Aim 1 is to conduct a Phase I trial of a microbicide for rectal use among MSM in Seattle. We will assess the baseline prevalence of rectal inflammation, and evaluate specific products with respect to their safety (rectal disruption and inflammation) and assess surrogate measures of possible efficacy (e.g. assessing relative impact of microbicides on HIV rectal shedding in HIV-infected MSM). Aim 2 is to continue a randomized trial of a 10-session behavioral counseling intervention (EXPLORE) among 725 high-risk HIV-negative MSM recruited in Seattle. Aim 3 is to assess the feasibility of adding a MSM-targeted intervention to a planned randomized community-level STD prevention trial in 24 Peruvian cities with 50,000-600,000 population and HIV prevalence of 2-10 percent among MSM. Aim 4 is to prospectively determine HIV incidence, behavioral and biologic risk factors (e.g. STDs) for HIV infection among MSM in Lima. Specifically, the investigators propose to: (a) assess the mechanism of HSV as a cofactor for HIV acquisition and determine the feasibility of daily antiviral suppressive therapy as a component of an STD intervention through a Phase I study, and (b) determine the role of high-risk bisexual men as a "bridging population" who may transmit HIV and STDs to women in Peru by analyzing sexual networks of MSM. Aim 5 is to assess biologic factors that influence HIV transmission in discordant MSM couples in Seattle and Lima, through studying effects of HAART and anogenital inflammation on HIV shedding, specifically: (1) the likelihood of transmission by viral load in blood, genital and rectal compartments, (2) whether HIV-1 cell-free or cell- associated virus is associated with transmission, and (3) the relationship of genital viral load relative to genital tract inflammation and drug susceptibility.